10.6084/M9.FIGSHARE.C.6273268.V1
Anne Vaiman
Anne
Vaiman
Animal Genetics and Integrative Biology Unit
Sébastien Fritz
Sébastien
Fritz
Animal Genetics and Integrative Biology Unit
Christian Beauvallet
Christian
Beauvallet
Animal Genetics and Integrative Biology Unit
Mekki Boussaha
Mekki
Boussaha
Animal Genetics and Integrative Biology Unit
Cécile Grohs
Cécile
Grohs
Animal Genetics and Integrative Biology Unit
Nathalie Daniel-Carlier
Nathalie
Daniel-Carlier
Animal Genetics and Integrative Biology Unit
Anne Relun
Anne
Relun
Oniris
Didier Boichard
Didier
Boichard
Animal Genetics and Integrative Biology Unit
Jean-Luc Vilotte
Jean-Luc
Vilotte
Animal Genetics and Integrative Biology Unit
University of Paris-Saclay
Amandine Duchesne
Amandine
Duchesne
0000-0002-9713-2274
Animal Genetics and Integrative Biology Unit
Mutation of the MYH3 gene causes recessive cleft palate in Limousine cattle
Abstract Background The palate is a structure separating the oral and nasal cavities and its integrity is essential for feeding and breathing. The total or partial opening of the palate is called a cleft palate and is a common malformation in mammals with environmental or hereditary aetiologies. Generally, it compromises life expectancy in the absence of surgical repair. A new form of non-syndromic cleft palate arose recently in Limousine cattle, with animals referred to the French National Observatory of Bovine Abnormalities since 2012. Since the number of affected animals has increased steadily, this study was undertaken to identify the cause of this disease. Results Based on pedigree analysis, occurrence of cleft palate in Limousine cattle was concordant with an autosomal recessive mode of inheritance. Genotyping of 16 affected animals and homozygosity mapping led to the identification of a single disease-associated haplotype on Bos taurus chromosome (BTA)19. The genome of two affected animals was sequenced, and their sequences were compared to the ARS-UCD1.2 reference genome to identify variants. The likely causal variants were compared to the variant database of the 1000 bull genome project and two fully linked mutations in exon 24 of the MYH3 (myosin heavy chain) gene were detected: a 1-bp non-synonymous substitution (BTA19:g.29609623A>G) and a 11-bp frameshift deletion (BTA19:g.29609605-29609615del). These two mutations were specific to the Limousine breed, with an estimated allele frequency of 2.4% and are predicted to be deleterious. The frameshift leads to a premature termination codon. Accordingly, mRNA and protein analyses in muscles from wild-type and affected animals revealed a decrease in MYH3 expression in affected animals, probably due to mRNA decay, as well as an absence of the MYH3 protein in these animals. MYH3 is mostly expressed in muscles, including craniofacial muscles, during embryogenesis, and its absence may impair palate formation. Conclusions We describe a new form of hereditary cleft palate in Limousine cattle. We identified two fully linked and deleterious mutations, ultimately leading to the loss-of-function of the MYH3 protein. The mutations were included on the Illumina EuroG10k v8 and EuroGMD v1 SNP chips and are used to set up a reliable eradication strategy in the French Limousine breed.
Genetics
figshare
2022
2022-10-31
2022-10-31
Collection
10.1186/s12711-022-00762-2
10.6084/m9.figshare.c.6273268
CC BY 4.0